Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Biochemistry, Hazara University, Mansehra, Pakistan.
Genet Test Mol Biomarkers. 2020 Apr;24(4):217-223. doi: 10.1089/gtmb.2019.0203. Epub 2020 Mar 27.
Frontonasal dysplasia (FND) is a rare developmental disorder characterized by mild to severe changes in skull and brain structures. It is a phenotypically variable and heterogeneous disorder. This study was designed to provide a clinical and genetic analysis of FND in a consanguineous family of Pakistani origin. Affected individuals in the family showed characteristic features of frontonasal dysplasia type-2 (FND2), such as nasal bone hypoplasia, hypertelorism, and alopecia. Skull and brain imaging of affected members revealed ossification defects and various types of brain structural anomalies that created a split-brain. Sanger sequencing of the gene revealed a homozygous missense variant [NM_021926.4: c.652C>T; p.(Arg218Trp)] in three affected members who demonstrated severe craniofacial anomalies. Heterozygous carriers in the family showed mild FND2 phenotypes. Clinical and genetic analysis of a family, exhibiting FND2 phenotypes, revealed several previously unreported clinical features and a novel missense variant in the gene. These results will facilitate diagnosis and genetic counseling of the FND patients in the Pakistani population.
额鼻发育不全症（FND）是一种罕见的发育障碍，其特征为颅骨和脑部结构出现轻度至重度变化。它是一种表型多变且异质性的疾病。本研究旨在对一个巴基斯坦系谱的 FND 患者进行临床和遗传分析。 该家系中受累个体表现出额鼻发育不全 2 型（FND2）的典型特征，如鼻骨发育不全、眼距过宽和脱发。受累成员的颅骨和脑部成像显示骨化缺陷和各种类型的脑部结构异常，导致大脑裂。对 基因的 Sanger 测序在 3 名表现出严重颅面异常的受累个体中发现了纯合错义变异 [NM_021926.4: c.652C>T;p.(Arg218Trp)]。家系中的杂合携带者表现出轻度 FND2 表型。 对表现出 FND2 表型的家系进行临床和遗传分析，揭示了一些以前未报道过的临床特征和 基因中的一个新错义变异。这些结果将有助于巴基斯坦人群中 FND 患者的诊断和遗传咨询。
